Minims Pilocarpine

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Minims Pilocarpine uses


DESCRIPTION

Minims Pilocarpine hydrochloride tablets, USP contain Minims Pilocarpine hydrochloride, a cholinergic agonist for oral use. Minims Pilocarpine hydrochloride, USP is a hygroscopic, odorless, bitter tasting white crystal or powder, which is soluble in water and alcohol and virtually insoluble in most non-polar solvents. Minims Pilocarpine hydrochloride, USP with a chemical name of (3S-cis)-2(3H)-Furanone, 3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl) methyl] monohydrochloride, has a molecular weight of 244.72.

Each 5 mg Minims Pilocarpine Hydrochloride Tablet, USP for oral administration contains 5 mg of Minims Pilocarpine hydrochloride. Inactive ingredients in the tablet are microcrystalline cellulose and stearic acid, the tablet's film coating is: polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.

Each 7.5 mg Minims Pilocarpine Hydrochloride Tablet, USP for oral administration contains 7.5 mg of Minims Pilocarpine hydrochloride. Inactive ingredients in the tablet are microcrystalline cellulose and stearic acid, the tablet's film coating is: FD&C Blue #2/Indigo Carmine aluminum lake, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.

Chemical Structure

CLINICAL PHARMACOLOGY

Pharmacodynamics

Minims Pilocarpine is a cholinergic parasympathomimetic agent exerting a broad spectrum of pharmacologic effects with predominant muscarinic action. Minims Pilocarpine, in appropriate dosage, can increase secretion by the exocrine glands. The sweat, salivary, lacrimal, gastric, pancreatic, and intestinal glands and the mucous cells of the respiratory tract may be stimulated. When applied topically to the eye as a single dose it causes miosis, spasm of accommodation, and may cause a transitory rise in intraocular pressure followed by a more persistent fall. Dose-related smooth muscle stimulation of the intestinal tract may cause increased tone, increased motility, spasm, and tenesmus. Bronchial smooth muscle tone may increase. The tone and motility of urinary tract, gallbladder, and biliary duct smooth muscle may be enhanced. Minims Pilocarpine may have paradoxical effects on the cardiovascular system. The expected effect of a muscarinic agonist is vasodepression, but administration of Minims Pilocarpine may produce hypertension after a brief episode of hypotension. Bradycardia and tachycardia have both been reported with use of Minims Pilocarpine.

In a study of 12 healthy male volunteers there was a dose-related increase in unstimulated salivary flow following single 5 and 10 mg oral doses of Minims Pilocarpine hydrochloride tablets. This effect of Minims Pilocarpine on salivary flow was time-related with an onset at 20 minutes and a peak effect at 1 hour with a duration of 3 to 5 hours.

Head & Neck Cancer Patients

In a 12 week randomized, double-blind, placebo-controlled study in 207 patients (placebo, N=65; 5 mg, N=73; 10 mg, N=69), increases from baseline (means 0.072 and 0.112 mL/min, ranges −0.690 to 0.728 and −0.380 to 1.689) of whole saliva flow for the 5 mg (63%) and 10 mg (90%) tablet, respectively, were seen 1 hour after the first dose of Minims Pilocarpine hydrochloride tablets. Increases in unstimulated parotid flow were seen following the first dose (means 0.025 and 0.046 mL/min, ranges 0 to 0.414 and −0.070 to 1.002 mL/min for the 5 and 10 mg dose, respectively). In this study, no correlation existed between the amount of increase in salivary flow and the degree of symptomatic relief.

Sjogren's Syndrome Patients

In two 12 week randomized, double-blind, placebo-controlled studies in 629 patients, the ability of Minims Pilocarpine hydrochloride tablets to stimulate saliva production was assessed. In these trials using varying doses of Minims Pilocarpine hydrochloride tablets (2.5-7.5 mg), the rate of saliva production was plotted against time. An Area Under the Curve (AUC) representing the total amount of saliva produced during the observation interval was calculated. Relative to placebo, an increase in the amount of saliva being produced was observed following the first dose of Minims Pilocarpine hydrochloride tablets and was maintained throughout the duration (12 weeks) of the trials in an approximate dose response fashion (See Clinical Studies section).

Pharmacokinetics

In a multiple-dose pharmacokinetic study in male volunteers following 2 days of 5 or 10 mg of oral Minims Pilocarpine hydrochloride tablets given at 8 a.m., noontime, and 6 p.m., the mean elimination half-life was 0.76 hours for the 5 mg dose and 1.35 hours for the 10 mg dose. Tmax values were 1.25 hours and 0.85 hours. Cmax values were 15 ng/mL and 41 ng/mL. The AUC trapezoidal values were 33 h(ng/mL) and 108 h(ng/mL), respectively, for the 5 and 10 mg doses following the last 6 hour dose.

Pharmacokinetics in elderly male volunteers (N = 11) were comparable to those in younger men. In five healthy elderly female volunteers, the mean Cmax and AUC were approximately twice that of elderly males and young normal male volunteers.

When taken with a high fat meal by 12 healthy male volunteers, there was a decrease in the rate of absorption of Minims Pilocarpine from Minims Pilocarpine hydrochloride tablets. Mean Tmax's were 1.47 and 0.87 hours, and mean Cmax's were 51.8 and 59.2 ng/mL for fed and fasted, respectively.

Limited information is available about the metabolism and elimination of Minims Pilocarpine in humans. Inactivation of Minims Pilocarpine is thought to occur at neuronal synapses and probably in plasma. Minims Pilocarpine and its minimally active or inactive degradation products, including pilocarpic acid, are excreted in the urine. Minims Pilocarpine does not bind to human or rat plasma proteins over a concentration range of 5 to 25,000 ng/mL. The effect of Minims Pilocarpine on plasma protein binding of other drugs has not been evaluated.

In patients with mild to moderate hepatic impairment (N=12), administration of a single 5 mg dose resulted in a 30% decrease in total plasma clearance and a doubling of exposure (as measured by AUC). Peak plasma levels were also increased by about 30% and half-life was increased to 2.1 hrs.

There were no significant differences in the pharmacokinetics of oral Minims Pilocarpine in volunteer subjects (N=8) with renal insufficiency (mean creatinine clearances 25.4 mL/min; range 9.8 – 40.8 mL/min) compared to the pharmacokinetics previously observed in normal volunteers.

Clinical Studies

Head & Neck Cancer Patients

A 12 week randomized, double-blind, placebo-controlled study in 207 patients was conducted in patients whose mean age was 58.5 years with a range of 19 to 77; the racial distribution was Caucasian 95%, Black 4%, and other 1%. In this population, a statistically significant improvement in mouth dryness occurred in the 5 and 10 mg Minims Pilocarpine hydrochloride tablet treated patients compared to placebo treated patients. The 5 and 10 mg treated patients could not be distinguished. (See Pharmacodynamics section for flow study details.)

Another 12 week, double-blind, randomized, placebo-controlled study was conducted in 162 patients whose mean age was 57.8 years with a range of 27 to 80; the racial distribution was Caucasian 88%, Black 10%, and other 2%. The effects of placebo were compared to 2.5 mg three times a day of Minims Pilocarpine hydrochloride tablets for 4 weeks followed by adjustment to 5 mg three times a day and 10 mg three times a day. Lowering of the dose was necessary because of adverse events in 3 of 67 patients treated with 5 mg of Minims Pilocarpine hydrochloride tablets and in 7 of 66 patients treated with 10 mg of Minims Pilocarpine hydrochloride tablets. After 4 weeks of treatment, 2.5 mg of Minims Pilocarpine hydrochloride tablets three times a day was comparable to placebo in relieving dryness. In patients treated with 5 mg and 10 mg of Minims Pilocarpine hydrochloride tablets, the greatest improvement in dryness was noted in patients with no measurable salivary flow at baseline.

In both studies, some patients noted improvement in the global assessment of their dry mouth, speaking without liquids, and a reduced need for supplemental oral comfort agents.

In the two placebo-controlled clinical trials, the most common adverse events related to drug, and increasing in rate as dose increases, were sweating, nausea, rhinitis, diarrhea, chills, flushing, urinary frequency, dizziness, and asthenia. The most common adverse experience causing withdrawal from treatment was sweating (5 mg t.i.d. ≤1%; 10 mg t.i.d. =12%).

Sjogren's Syndrome Patients

Two separate studies were conducted in patients with primary or secondary Sjogren's Syndrome. In both studies, the majority of patients best fit the European criteria for having primary Sjogren's Syndrome. ["Criteria for the Classification of Sjogren's Syndrome" (Vitali C, Bombardieri S, Moutsopoulos HM, et al: Preliminary criteria for the classification of Sjogren's syndrome. Arthritis Rheum 36:340-347, 1993.)]

A twelve week, randomized, double-blind, parallel-group, placebo-controlled study was conducted in 256 patients (14 men, 242 women) whose mean age was 57 years with a range of 24 to 85 years. The racial distribution was as follows: Caucasian 91%, Black 6%, and other 3%.

The effects of placebo were compared with those of Minims Pilocarpine hydrochloride tablets 5 mg four times a day (20 mg/day) for 6 weeks. At 6 weeks, the patients' dosage was increased from 5 mg Minims Pilocarpine hydrochloride tablets q.i.d. to 7.5 mg q.i.d. The data collected during the first 6 weeks of the trial were evaluated for safety and efficacy, and the data of the second 6 weeks of the trial were used to provide additional evidence of safety.

After 6 weeks of treatment, statistically significant global improvement of dry mouth was observed compared to placebo. "Global improvement" is defined as a score of 55 mm or more on a 100 mm visual analogue scale in response to the question, "Please rate your present condition of dry mouth (xerostomia) compared with your condition at the start of this study. Consider the changes to your dry mouth and other symptoms related to your dry mouth that have occurred since you have taken this medication." Patients' assessments of specific dry mouth symptoms such as severity of dry mouth, mouth discomfort, ability to speak without water, ability to sleep without drinking water, ability to swallow food without drinking, and a decreased use of saliva substitutes were found to be consistent with the significant global improvement described.

Another 12 week randomized, double-blind, parallel-group, placebo-controlled study was conducted in 373 patients (16 men, 357 women) whose mean age was 55 years with a range of 21 to 84. The racial distribution was Caucasian 80%, Oriental 14%, Black 2%, and 4% of other origin. The treatment groups were 2.5 mg Minims Pilocarpine tablets, 5 mg Minims Pilocarpine hydrochloride tablets, and placebo. All treatments were administered on a four times a day regimen.

After 12 weeks of treatment, statistically significant global improvement of dry mouth was observed at a dose of 5 mg compared with placebo. The 2.5 mg (10mg/day) group was not significantly different than placebo. However, a subgroup of patients with rheumatoid arthritis tended to improve in global assessments at both the 2.5 mg q.i.d. (9 patients) and 5 mg q.i.d. (16 patients) dose (10-20 mg/day). The clinical significance of this finding is unknown.

Patients' assessments of specific dry mouth symptoms such as severity of dry mouth, mouth discomfort, ability to sleep without drinking water, and decreased use of saliva substitutes were also found to be consistent with the significant global improvement described when measured after 6 weeks and 12 weeks of Minims Pilocarpine hydrochloride tablets use.

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INDICATIONS AND USAGE

Minims Pilocarpine hydrochloride tablets, USP are indicated for 1) the treatment of symptoms of dry mouth from salivary gland hypofunction caused by radiotherapy for cancer of the head and neck; and 2) the treatment of symptoms of dry mouth in patients with Sjogren's syndrome.

CONTRAINDICATIONS

Minims Pilocarpine hydrochloride tablets are contraindicated in patients with uncontrolled asthma, known hypersensitivity to Minims Pilocarpine, and when miosis is undesirable, e.g., in acute iritis and in narrow-angle (angle closure) glaucoma.

WARNINGS

Cardiovascular Disease

Patients with significant cardiovascular disease may be unable to compensate for transient changes in hemodynamics or rhythm induced by Minims Pilocarpine. Pulmonary edema has been reported as a complication of Minims Pilocarpine toxicity from high ocular doses given for acute angle-closure glaucoma. Minims Pilocarpine should be administered with caution in and under close medical supervision of patients with significant cardiovascular disease.

Ocular

Ocular formulations of Minims Pilocarpine have been reported to cause visual blurring which may result in decreased visual acuity, especially at night and in patients with central lens changes, and to cause impairment of depth perception. Caution should be advised while driving at night or performing hazardous activities in reduced lighting.

Pulmonary Disease

Minims Pilocarpine has been reported to increase airway resistance, bronchial smooth muscle tone, and bronchial secretions. Minims Pilocarpine hydrochloride should be administered with caution to and under close medical supervision in patients with controlled asthma, chronic bronchitis, or chronic obstructive pulmonary disease requiring pharmacotherapy.

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PRECAUTIONS

General

Minims Pilocarpine toxicity is characterized by an exaggeration of its parasympathomimetic effects. These may include: headache, visual disturbance, lacrimation, sweating, respiratory distress, gastrointestinal spasm, nausea, vomiting, diarrhea, atrioventricular block, tachycardia, bradycardia, hypotension, hypertension, shock, mental confusion, cardiac arrhythmia, and tremors.

The dose-related cardiovascular pharmacologic effects of Minims Pilocarpine include hypotension, hypertension, bradycardia, and tachycardia.

Minims Pilocarpine should be administered with caution to patients with known or suspected cholelithiasis or biliary tract disease. Contractions of the gallbladder or biliary smooth muscle could precipitate complications including cholecystitis, cholangitis, and biliary obstruction.

Minims Pilocarpine may increase ureteral smooth muscle tone and could theoretically precipitate renal colic, particularly in patients with nephrolithiasis.

Cholinergic agonists may have dose-related central nervous system effects. This should be considered when treating patients with underlying cognitive or psychiatric disturbances.

Hepatic Insufficiency

Based on decreased plasma clearance observed in patients with moderate hepatic impairment, the starting dose in these patients should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency (Child-Pugh score of 5-6) do not require dosage reductions. To date, pharmacokinetic studies in subjects with severe hepatic impairment (Child-Pugh score of 10-15) have not been carried out. The use of Minims Pilocarpine in these patients is not recommended.

Clinical and Biochemical

Measurements

Points Scored for

Increasing Abnormality

1 2 3
Encephalopathy (grade)According to grading of Trey C, Burns D, and Saunders S. Treatment of hepatic coma by exchange blood transfusion. N Engl J Med. 1966; 274:473-481. None 1 and 2 3 and 4
Ascites Absent Slight Moderate
Bilirubin (mg. Per 100 ml.) 1-2 2-3 >3
Albumin (g. per 100 ml.) 3-5 2.8-3.5 <2.8
Prothrombin time (sec. Prolonged) 1-4 4-6 >6
For primary biliary cirrhosis:-

Bilirubin (mg. Per 100 ml.)

1-4 4-10 >10

Reference: Pugh, RNH, Murray-Lyon, IM, Dawson, JL Pietroni, MC, Williams, R. Transection of the Oesophagus for Bleeding Oesophageal Varices, Brit. J. Surg. 1973;60:646-9.

Information for Patients

Patients should be informed that Minims Pilocarpine may cause visual disturbances, especially at night, that could impair their ability to drive safely.

If a patient sweats excessively while taking Minims Pilocarpine hydrochloride and cannot drink enough liquid, the patient should consult a physician. Dehydration may develop.

Drug Interactions

Minims Pilocarpine should be administered with caution to patients taking beta adrenergic antagonists because of the possibility of conduction disturbances. Drugs with parasympathomimetic effects administered concurrently with Minims Pilocarpine would be expected to result in additive pharmacologic effects.

Minims Pilocarpine might antagonize the anticholinergic effects of drugs used concomitantly. These effects should be considered when anticholinergic properties may be contributing to the therapeutic effect of concomitant medication.

While no formal drug interaction studies have been performed, the following concomitant drugs were used in at least 10% of patients in either or both Sjogren's efficacy studies: acetylsalicylic acid, artificial tears, calcium, conjugated estrogens, hydroxychloroquine sulfate, ibuprofen, levothyroxine sodium, medroxyprogesterone acetate, methotrexate, multivitamins, naproxen, omeprazole, paracetamol, and prednisone.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime oral carcinogenicity studies were conducted in CD-1 mice and Sprague-Dawley rats. Minims Pilocarpine did not induce tumors in mice at any dosage studied (up to 30 mg/kg/day, which yielded a systemic exposure approximately 50 times larger than the maximum systemic exposure observed clinically). In rats, a dosage of 18 mg/kg/day, which yielded a systemic exposure approximately 100 times larger than the maximum systemic exposure observed clinically, resulted in a statistically significant increase in the incidence of benign pheochromocytomas in both males and females, and a statistically significant increase in the incidence of hepatocellular adenomas in female rats. The tumorigenicity observed in rats was observed only at a large multiple of the maximum labeled clinical dose, and may not be relevant to clinical use.

No evidence that Minims Pilocarpine has the potential to cause genetic toxicity was obtained in a series of studies that included: 1) bacterial assays (Salmonella and E. coli) for reverse gene mutations; 2) an in vitro chromosome aberration assay in a Chinese hamster ovary cell line; 3) an in vivo chromosome aberration assay (micronucleus test) in mice; and 4) a primary DNA damage assay (unscheduled DNA synthesis) in rat hepatocyte primary cultures.

Oral administration of Minims Pilocarpine to male and female rats at a dosage of 18 mg/kg/day, which yielded a systemic exposure approximately 100 times larger than the maximum systemic exposure observed clinically, resulted in impaired reproductive function, including reduced fertility, decreased sperm motility, and morphologic evidence of abnormal sperm. It is unclear whether the reduction in fertility was due to effects on male animals, female animals, or both males and females. In dogs, exposure to Minims Pilocarpine at a dosage of 3 mg/kg/day (approximately 3 times the maximum recommended human dose when compared on the basis of body surface area (mg/m2) estimates) for six months resulted in evidence of impaired spermatogenesis. The data obtained in these studies suggest that Minims Pilocarpine may impair the fertility of male and female humans. Minims Pilocarpine hydrochloride tablets should be administered to individuals who are attempting to conceive a child only if the potential benefit justifies potential impairment of fertility.

Pregnancy

Teratogenic effects

Pregnancy Category C

Minims Pilocarpine was associated with a reduction in the mean fetal body weight and an increase in the incidence of skeletal variations when given to pregnant rats at a dosage of 90 mg/kg/day estimates). These effects may have been secondary to maternal toxicity. In another study, oral administration of Minims Pilocarpine to female rats during gestation and lactation at a dosage of 36 mg/kg/day (approximately 10 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (mg/m2) estimates) resulted in an increased incidence of stillbirths; decreased neonatal survival and reduced mean body weight of pups were observed at dosages of 18 mg/kg/day (approximately 5 times the maximum recommended dose for a 50 kg human when compared on the basis of body surface area (mg/m2) estimates) and above. There are no adequate and well-controlled studies in pregnant women. Minims Pilocarpine hydrochloride tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Minims Pilocarpine hydrochloride tablets, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Head and Neck Cancer Patients

In the placebo-controlled clinical trials the mean age of patients was approximately 58 years (range 19 to 80). Of these patients, 97/369 (61/217 receiving Minims Pilocarpine) were over the age of 65 years. In the healthy volunteer studies, 15/150 subjects were over the age of 65 years. In both study populations, the adverse events reported by those over 65 years and those 65 years and younger were comparable. Of the 15 elderly volunteers (5 women, 10 men), the 5 women had higher Cmax's and AUC's than the men. (See Pharmacokinetics section.)

Sjogren's Syndrome Patients

In the placebo-controlled clinical trials (see Clinical Studies section), the mean age of patients was approximately 55 years (range 21 to 85). The adverse events reported by those over 65 years and those 65 years and younger were comparable except for notable trends for urinary frequency, diarrhea, and dizziness (see ADVERSE REACTIONS section).

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ADVERSE REACTIONS

Head & Neck Cancer Patients

In controlled studies, 217 patients received Minims Pilocarpine, of whom 68% were men and 32% were women. Race distribution was 91% Caucasian, 8% Black, and 1% of other origin. Mean age was approximately 58 years. The majority of patients were between 50 and 64 years, 33% were 65 years and older and 16% were younger than 50 years of age.

The most frequent adverse experiences associated with Minims Pilocarpine hydrochloride tablets were a consequence of the expected pharmacologic effects of Minims Pilocarpine.

Adverse Event Minims Pilocarpine HCl Placebo
10 mg t.i.d.

(30 mg/day)

5 mg t.i.d.

(15 mg/day)

(t.i.d.)
N=121 N=141 N=152
Sweating 68% 29% 9%
Nausea 15 6 4
Rhinitis 14 5 7
Diarrhea 7 4 5
Chills 15 3 <1
Flushing 13 8 3
Urinary Frequency 12 9 7
Dizziness 12 5 4
Asthenia 12 6 3

In addition, the following adverse events (≥3% incidence) were reported at dosages of 15-30 mg/day in the controlled clinical trials:

Adverse Event Minims Pilocarpine HCl Placebo
5-10 mg t.i.d.

(15-30 mg/day)

(t.i.d.)
N=212 N=152
Headache 11% 8%
Dyspepsia 7 5
Lacrimation 6 8
Edema 5 4
Abdominal Pain 4 4
Amblyopia 4 2
Vomiting 4 1
Pharyngitis 3 8
Hypertension 3 1

The following events were reported with treated head and neck cancer patients at incidences of 1% to 2% at dosages of 7.5 to 30 mg/day: abnormal vision, conjunctivitis, dysphagia, epistaxis, myalgias, pruritus, rash, sinusitis, tachycardia, taste perversion, tremor, voice alteration.

The following events were reported rarely in treated head and neck cancer patients (<1%): Causal relation is unknown.

Body as a whole: body odor, hypothermia, mucous membrane abnormality

Cardiovascular: bradycardia, ECG abnormality, palpitations, syncope

Digestive: anorexia, increased appetite, esophagitis, gastrointestinal disorder, tongue disorder

Hematologic: leukopenia, lymphadenopathy

Nervous: anxiety, confusion, depression, abnormal dreams, hyperkinesia, hypesthesia, nervousness, paresthesias, speech disorder, twitching

Respiratory: increased sputum, stridor, yawning

Skin: seborrhea

Special senses: deafness, eye pain, glaucoma

Urogenital: dysuria, metrorrhagia, urinary impairment

In long-term treatment were two patients with underlying cardiovascular disease of whom one experienced a myocardial infarct and another episode of syncope. The association with drug is uncertain.

Sjogren's Syndrome Patients

In controlled studies, 376 patients received Minims Pilocarpine, of whom 5% were men and 95% were women. Race distribution was 84% Caucasian, 9% Oriental, 3% Black, and 4% of other origin. Mean age was 55 years. The majority of patients were between 40 and 69 years (70%), 16% were 70 years and older and 14% were younger than 40 years of age. Of these patients, 161/629 (89/376 receiving Minims Pilocarpine) were over the age of 65 years. The adverse events reported by those over 65 years and those 65 years and younger were comparable except for notable trends for urinary frequency, diarrhea, and dizziness. The incidences of urinary frequency and diarrhea in the elderly were about double those in the non-elderly. The incidence of dizziness was about three times as high in the elderly as in the non-elderly. These adverse experiences were not considered to be serious. In the 2 placebo-controlled studies, the most common adverse events related to drug use were sweating, urinary frequency, chills, and vasodilatation (flushing). The most commonly reported reason for patient discontinuation of treatment was sweating. Expected pharmacologic effects of Minims Pilocarpine include the following adverse experiences associated with Minims Pilocarpine hydrochloride tablets:

Adverse Event Minims Pilocarpine HCl Placebo
5 mg q.i.d.

(20 mg/day)

(q.i.d.)
N=255 N=253
Sweating 40% 7%
Urinary Frequency 10 4
Nausea 9 9
Flushing 9 2
Rhinitis 7 8
Diarrhea 6 7
Chills 4 2
Increased Salivation 3 0
Asthenia 2 2

In addition, the following adverse events (≥3% incidence) were reported at dosages of 20 mg/day in the controlled clinical trials:

Adverse Event Minims Pilocarpine HCl Placebo
5 mg q.i.d.

(20 mg/day)

(q.i.d.)
N=255 N=253
Headache 13% 19%
Flu Syndrome 9 9
Dyspepsia 7 7
Dizziness 6 7
Pain 4 2
Sinusitis 4 5
Abdominal Pain 3 4
Vomiting 3 1
Pharyngitis 2 5
Rash 2 3
Infection 2 6

The following events were reported in Sjogren's patients at incidences of 1% to 2% at dosing of 20 mg/day: accidental injury, allergic reaction, back pain, blurred vision, constipation, increased cough, edema, epistaxis, face edema, fever, flatulence, glossitis, lab test abnormalities, including chemistry, hematology, and urinalysis, myalgia, palpitation, pruritus, somnolence, stomatitis, tachycardia, tinnitus, urinary incontinence, urinary tract infection, vaginitis.

The following events were reported rarely in treated Sjogren's patients (<1%) at dosing of 10-30 mg/day: Causal relation is unknown.

Body as a whole: chest pain, cyst, death, moniliasis, neck pain, neck rigidity, photosensitivity reaction

Cardiovascular: angina pectoris, arrhythmia, ECG abnormality, hypotension, hypertension, intracranial hemorrhage, migraine, myocardial infarction

Digestive: anorexia, bilirubinemia, cholelithiasis, colitis, dry mouth, eructation, gastritis, gastroenteritis, gastrointestinal disorder, gingivitis, hepatitis, abnormal liver function tests, melena, nausea & vomiting, pancreatitis, parotid gland enlargement, salivary gland enlargement, sputum increased, taste loss, tongue disorder, tooth disorder

Hematologic: hematuria, lymphadenopathy, abnormal platelets, thrombocythemia, thrombocytopenia, thrombosis, abnormal WBC

Metabolic and Nutritional: peripheral edema, Hypoglycemia

Musculoskeletal: arthralgia, arthritis, bone disorder, spontaneous bone fracture, pathological fracture, myasthenia, tendon disorder, tenosynovitis

Nervous: aphasia, confusion, depression, abnormal dreams, emotional lability, hyperkinesia, hypesthesia, insomnia, leg cramps, nervousness, parethesias, abnormal thinking, tremor

Respiratory: bronchitis, dyspnea, hiccup, laryngismus, laryngitis, pneumonia, viral infection, voice alteration

Skin: alopecia, contact dermatitis, dry skin, eczema, erythema nodosum, exfoliative dermatitis, herpes simplex, skin ulcer, vesiculobullous rash

Special senses: cataract, conjunctivitis, dry eyes, ear disorder, ear pain, eye disorder, eye hemorrhage, glaucoma, lacrimation disorder, retinal disorder, taste perversion, abnormal vision

Urogenital: breast pain, dysuria, mastitis, menorrhagia, metrorrhagia, ovarian disorder, pyuria, salpingitis, urethral pain, urinary urgency, vaginal hemorrhage, vaginal moniliasis

The following adverse experiences have been reported rarely with ocular Minims Pilocarpine: A-V block, agitation, ciliary congestion, confusion, delusion, depression, dermatitis, middle ear disturbance, eyelid twitching, malignant glaucoma, iris cysts, macular hole, shock, and visual hallucination.

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MANAGEMENT OF OVERDOSE

Fatal overdosage with Minims Pilocarpine has been reported in the scientific literature at doses presumed to be greater than 100 mg in two hospitalized patients. 100 mg of Minims Pilocarpine is considered potentially fatal. Overdosage should be treated with atropine titration (0.5 mg to 1.0 mg given subcutaneously or intravenously) and supportive measures to maintain respiration and circulation. Epinephrine (0.3 mg to 1.0 mg, subcutaneously or intramuscularly) may also be of value in the presence of severe cardiovascular depression or bronchoconstriction. It is not known if Minims Pilocarpine is dialyzable.

DOSAGE AND ADMINISTRATION

Regardless of the indication, the starting dose in patients with moderate hepatic impairment should be 5 mg twice daily, followed by adjustment based on therapeutic response and tolerability. Patients with mild hepatic insufficiency do not require dosage reductions. The use of Minims Pilocarpine in patients with severe hepatic insufficiency is not recommended. If needed, refer to the Hepatic Insufficiency subsection of the Precautions section of this label for definitions of mild, moderate and severe hepatic impairment.

Head & Neck Cancer Patients

The recommended initial dose of Minims Pilocarpine hydrochloride tablets is 5 mg taken three times a day. Dosage should be titrated according to therapeutic response and tolerance. The usual dosage range is up to 15-30 mg per day. Although early improvement may be realized, at least 12 weeks of uninterrupted therapy with Minims Pilocarpine hydrochloride tablets may be necessary to assess whether a beneficial response will be achieved. The incidence of the most common adverse events increases with dose. The lowest dose that is tolerated and effective should be used for maintenance.

Sjogren's Syndrome Patients

The recommended dose of Minims Pilocarpine hydrochloride tablets is 5 mg taken four times a day. Efficacy was established by 6 weeks of use.

HOW SUPPLIED

Minims Pilocarpine hydrochloride tablets USP, 5 mg are white, film coated, round tablets, debossed LAN on one side and 1313 on the other side. Each tablet contains 5 mg Minims Pilocarpine hydrochloride. They are supplied as follows:

Bottles of 100; NDC 0527-1313-01

Store at 20°- 25°C(68°-77°F).

Minims Pilocarpine hydrochloride tablets USP, 7.5 mg are blue, film coated, round tablets, debossed LCI on one side and 1407 on the other side. Each tablet contains 7.5 mg Minims Pilocarpine hydrochloride. They are supplied as follows:

Bottles of 100; NDC 0527-1407-01

Store at 20°- 25°C(68°-77°F).

Distributed by:

Lannett Company, Inc.

Philadelphia, PA 19136

Made in the USA

CIB70322B

Revised 03/16

Minims Pilocarpine pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Minims Pilocarpine available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Minims Pilocarpine destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Minims Pilocarpine Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Minims Pilocarpine pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."PILOCARPINE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "pilocarpine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "pilocarpine". http://www.drugbank.ca/drugs/DB0108... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Minims Pilocarpine?

Depending on the reaction of the Minims Pilocarpine after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Minims Pilocarpine not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Minims Pilocarpine addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Minims Pilocarpine, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Minims Pilocarpine consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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